We are studying the genetic basis of a variety of skin disorders, including six disorders of cornification (epidermolytic hyperkeratosis, lamellar ichthyosis and congenital ichthyosiform erythroderma, Darier's disease, Hailey-Hailey disease, and ichthyosis vulgaris) and two disorders predisposing to skin cancer (basal cell nevus syndrome, familial malignant melanoma). Patients and their families are recruited for study. They travel to the NIH clinics (or rarely we travel to them) to enable our research group to perform detailed family and medical histories, skin examinations, skin biopsies, phlebotomy, and clinical photography. DNA is extracted from patient's blood and permanent cell lines established. Skin samples are used to confirm diagnoses and to investigate ultrastructural abnormalities specific to each disease. Clinical heterogeneity (different clinical appearances of the "same" disease) is investigated using the information collected. DNA-based polymorphisms (i.e. RFLPs, PCR) are used for linkage studies to determine the chromosomal location of the skin disease locus.